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@article{Piquereau:2019:10.3390/ijms20071527,
author = {Piquereau, J and Boet, A and Pechoux, C and Antigny, F and Lambert, M and Gressette, M and Ranchoux, B and Gambaryan, N and Domergue, V and Mumby, S and Montani, D and Adcock, IM and Humbert, M and Garnier, A and Rucker-Martin, C and Perros, F},
doi = {10.3390/ijms20071527},
journal = {International Journal of Molecular Sciences},
pages = {1--16},
title = {The BET bromodomain inhibitor I-BET-151 induces structural and functional alterations of the heart mitochondria in healthy male mice and rats},
url = {http://dx.doi.org/10.3390/ijms20071527},
volume = {20},
year = {2019}
}

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TY  - JOUR
AB  - The bromodomain and extra-terminal domain family inhibitors (BETi) are a promising new class of anticancer agents. Since numerous anticancer drugs have been correlated to cardiomyopathy, and since BETi can affect non-cancerous tissues, we aimed to investigate in healthy animals any ultrastructural BETi-induced alterations of the heart as compared to skeletal muscle. Male Wistar rats were either treated during 3 weeks with I-BET-151 (2 or 10 mg/kg/day) (W3) or treated for 3 weeks then allowed to recover for another 3 weeks (W6) (3-weeks drug washout). Male C57Bl/6J mice were only treated during 5 days (50 mg/kg/day). We demonstrated the occurrence of ultrastructural alterations and progressive destruction of cardiomyocyte mitochondria after I-BET-151 exposure. Those mitochondrial alterations were cardiac muscle-specific, since the skeletal muscles of exposed animals were similar in ultrastructure presentation to the non-exposed animals. I-BET-151 decreased the respiration rate of heart mitochondria in a dose-dependent manner. At the higher dose, it also decreased mitochondrial mass, as evidenced by reduced right ventricular citrate synthase content. I-BET-151 reduced the right and left ventricular fractional shortening. The concomitant decrease in the velocity-time-integral in both the aorta and the pulmonary artery is also suggestive of an impaired heart function. The possible context-dependent cardiac side effects of these drugs have to be appreciated. Future studies should focus on the basic mechanisms of potential cardiovascular toxicities induced by BETi and strategies to minimize these unexpected complications.
AU  - Piquereau,J
AU  - Boet,A
AU  - Pechoux,C
AU  - Antigny,F
AU  - Lambert,M
AU  - Gressette,M
AU  - Ranchoux,B
AU  - Gambaryan,N
AU  - Domergue,V
AU  - Mumby,S
AU  - Montani,D
AU  - Adcock,IM
AU  - Humbert,M
AU  - Garnier,A
AU  - Rucker-Martin,C
AU  - Perros,F
DO  - 10.3390/ijms20071527
EP  - 16
PY  - 2019///
SN  - 1422-0067
SP  - 1
TI  - The BET bromodomain inhibitor I-BET-151 induces structural and functional alterations of the heart mitochondria in healthy male mice and rats
T2  - International Journal of Molecular Sciences
UR  - http://dx.doi.org/10.3390/ijms20071527
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000464980400012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.mdpi.com/1422-0067/20/7/1527
UR  - http://hdl.handle.net/10044/1/77627
VL  - 20
ER  -

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